Sentynl Therapeutics, the US-based subsidiary of Zydus Lifesciences, has achieved a significant regulatory milestone with USFDA approval for ZYCUBO (copper histidinate), the first and only approved treatment for Menkes disease in the United States. This breakthrough addresses a critical unmet medical need for patients suffering from this rare, fatal genetic disorder that affects copper absorption and transport in the body.

Clinical Impact and Treatment Efficacy

ZYCUBO represents a life-changing therapy for pediatric patients with Menkes disease. The subcutaneous injectable formulation works by restoring copper homeostasis in affected children, addressing the fundamental metabolic dysfunction that characterizes this devastating condition.

Clinical trial results demonstrated remarkable efficacy:

Understanding Menkes Disease

Menkes disease is an X-linked recessive disorder caused by mutations in the ATP7A gene. The condition has an estimated birth prevalence as high as 1 in 8,664 live male births, making it a rare but significant pediatric health concern. Without treatment, patients typically experience severe neurological symptoms and face a life expectancy of less than three years, with most dying by age three.

Key characteristics of the disease include:

• Impaired copper absorption and transport
• Severe neurological manifestations
• Fatal progression without intervention
• Primarily affects male children due to X-linked inheritance

Regulatory Recognition and Development Timeline

The USFDA granted ZYCUBO multiple special designations, recognizing its importance in addressing an unmet medical need:

Sentynl acquired the ZYCUBO asset from Cyprium Therapeutics in 2023 and successfully advanced it through pivotal clinical studies to achieve this regulatory approval.

Strategic Significance for Zydus Lifesciences

This approval marks Zydus Lifesciences' entry into the rare disease therapeutic space, representing a strategic expansion beyond its traditional generics portfolio. Dr. Sharvil Patel, Managing Director of Zydus Lifesciences, emphasized the significance of this achievement, stating that "for the first time, patients have access to an approved therapy, offering hope where no options existed."

The company, which employs 29,000 people globally, aims to expand its rare disease portfolio through Sentynl's US platform. This approval demonstrates Zydus Lifesciences' commitment to innovation-led therapies and its capability to develop treatments for underserved patient populations.

It's important to note that ZYCUBO is not indicated for Occipital Horn Syndrome, ensuring appropriate use within its approved indication for Menkes disease treatment.

Zydus Lifesciences Limited has achieved a significant regulatory milestone with its US subsidiary Sentynl Therapeutics receiving FDA approval for ZYCUBO® (copper histidinate), the first and only approved therapy for Menkes disease in the United States. The company announced this breakthrough development in a press release filed with exchanges on Tuesday, January 13.

Addressing Critical Unmet Medical Need

Menkes disease represents a rare and often fatal genetic disorder caused by impaired copper transport in the body. The condition is an X-linked recessive disorder resulting from mutations in the ATP7A gene, which prevents proper absorption and transport of dietary copper. This leads to severe neurological damage and early mortality if left untreated, with most patients not surviving beyond two to three years of age.

Until this approval, no FDA-approved treatment options existed for Menkes disease patients in the United States, representing a critical gap in pediatric rare disease care.

Clinical Efficacy and Treatment Benefits

ZYCUBO® is formulated as a subcutaneous injectable treatment containing copper histidinate, designed to restore copper balance and maintain appropriate copper levels in affected patients. The FDA approval is supported by compelling clinical data demonstrating significant therapeutic benefits.

The clinical data shows a nearly 80% reduction in death risk for patients receiving early treatment with ZYCUBO® compared to an untreated external control group. Most significantly, median overall survival improved dramatically from 17.60 months in untreated patients to 177.10 months with ZYCUBO® treatment.

Leadership Perspectives and Regulatory Recognition

Dr. Sharvil P. Patel, Managing Director of Zydus Lifesciences, emphasized the transformative nature of this approval, stating it "marks a transformative moment for families affected by Menkes disease" and offers "hope where no options existed." Matt Heck, CEO of Sentynl, highlighted that the FDA approval serves as "compelling affirmation that a safe and effective therapy is now available for patients living with this devastating disease."

ZYCUBO® has received multiple regulatory designations from the FDA, including:

• Breakthrough Therapy designation
• Fast Track status
• Rare Pediatric Disease designation
• Orphan Drug status

Additionally, copper histidinate has been granted orphan designation by the European Medicines Agency, indicating broader international recognition of its therapeutic potential.

Strategic Acquisition and Market Performance

Sentynl acquired ZYCUBO® from Cyprium Therapeutics in 2023, representing a strategic move to expand Zydus Lifesciences' presence in the rare disease therapeutic space. The approval aligns with the company's focus on advancing innovative therapies for unmet medical needs globally.

As of 10:57 AM on the announcement day, Zydus Lifesciences shares were trading at ₹894.80, down 0.03% for the session. The stock has declined 7.60% over the past six months, though this FDA approval represents a significant positive development for the company's rare disease portfolio.